1. Lorena Bouzas Alfonsín Advanced Genetics 2017-2018
NUTRIGENOMICS
Lorena Bouzas Alfonsín
Advanced Genetics

2. Contents Introduction. Nutritional genomics Nutrigenetics
Nutritional epigenomics
Nutrigenomics
Nutrigenomics tools: present and future

3. NUTRITIONAL EPIGENOMICS
Nutritional genomics
Interactions genes - nutrients survival and reproduction
NUTRIGENETICS
NUTRIGENOMICS
NUTRITIONAL EPIGENOMICS

4. greater risk of lung cancer
Nutrigenetics
Genetic changes influence the response to nutrients
Example
reduce incidence of cancer
Polymorphism at codon 198
Substitution of proline to leucine
Pro/Pro
Pro/Leu %
greater risk of lung cancer
Leu/Leu %

5. Nutritional epigenetics
Nutrients cause modifications in the genome that don’t involve changes in the DNA sequence
Example
Vitamins B12, B6, niacin, riboflavin and minerals
Methylated DNA gene expression is silenced
Nutrients involved in DNA methylation
SAM for genome methylation
Nutritional deficiencies alter methylation patterns
Alteration of gene expression

6. Nutrigenomics Nutrigenomics
Nutrients influence gene expression, mainly through transcriptions factors (TFs)

7. preventative against cardiovascular disease
Nutrigenomics
Peroxisome proliferation activated receptors (PPARs)
- Fatty acid metabolism
- Ketogenesis
- Gluconeogenesis
- Amino acid metabolism
influence expression of genes involved in
ω-3 and ω6
fatty acids
Vitamin A derivates
Fatty acid synthesis
Fatty acid oxidation
lipoproteins cholesterol
Modulate genes involved in the metabolism of
Fibrates
plasma triglycerides
HDL cholesterol
preventative against cardiovascular disease
Kauwell, G. P. A., Emerging concepts in nutrigenomics: a preview of what is to come. Nutrition in Clinical Practice, 20(1), pp

8. Nutrigenomics
Müller, M. and Kersten, S., Nutrigenomics: goals and strategies. Nature Reviews Genetics, 4(4), pp

9. Nutrigenomics
Natural compounds have effects on cancer cells through targeting multiple cellular signalling pathways
Akt
NF-κB
Wnt
MAPK AR ER
Notch
p53
Examples
Epigallocatechin gallate (EGCG) a polyphenol presents in green tea
Inhibits phosphorylation of:
- Her-2/neu receptor
- Epidermal growth factor receptor (EGFR)
Reduce NF-κb pathway associated with breast cancer

10. Inhibitory effects on cancer cell growth
Nutrigenomics
Indol-3 carbinol (I3C) from glucosinolates of family Cruciferae
Modulate genes related to:
control of cell proliferation
cell cycle
apoptosis
signal transduction
oncogenesis
Curcumin presents in turmeric
Antiinflammatory and antioxidant effects
Cancer chemopreventive agent
Resveratrol
phytoalexin present in grapes, mulberries and peanuts
Lycopene
present in tomatoes
Inhibitory effects on cancer cell growth
Inhibit growth of various
cancer cells
- Induce apoptotic cell death

11. A traditional hypothesis-driven approach A system biology approach
Nutrigenomic tools
Genomic tools can be used in two complementary strategies:
A traditional hypothesis-driven approach
A system biology approach
Genome wide discovery of target genes and the regulatory pathways through which diet influences homeostasis
Identify molecular biomarkers associated
with early changes of homeostatic control

12. Nutrigenomic tools
Present
Main investigate strategies to discover dietary target genes
and the pathways affected:
Transgenic and knockout
mouse models
In vitro experiments
- Inducible expression systems
- RNA interference (RNAi)
- Transdominant negative adenoviral constructs (tdnAd)
Modulate expression levels
and functionality of nutrient-sensor systems
Müller, M. and Kersten, S., Nutrigenomics: goals and strategies. Nature Reviews Genetics, 4(4), pp

13. Nutrigenomic tools Future
Collect “healthy” diet-related expression signatures
Compare with stress signatures derived from experiments
Identify early biomarkers that could warn about future serious conditions
Design dietary interventions to:
- prevent these conditions in risk groups
regain homeostatic control
Müller, M. and Kersten, S., Nutrigenomics: goals and strategies. Nature Reviews Genetics, 4(4), pp

14. References
DeBusk, R., The role of Nutritional Genomics in Developing an Optimal Diet for Humans. Nutrition in Clinical Practice, 25(6), pp
Farhud, D. D. and Zarif Yeganeh, D., Nutrigenomics and Nutrigenetics. Iranian Journal of Public Health, 39(4), pp
Kauwell, G. P. A., Emerging concepts in nutrigenomics: a preview of what is to come. Nutrition in Clinical Practice, 20(1), pp
Müller, M. and Kersten, S., Nutrigenomics: goals and strategies. Nature Reviews Genetics, 4(4), pp
Sarkar, F. H., Yiwei, L., Li, Y., Wang, Z., Kong, D., Cellular signaling perturbation by natural products. Cellular signaling, 21(11), pp
Singh-Dang, T., Walker, M., Ford, D. and Valentine, R. A., Nutrigenomics: the role of nutrients in gene expression. Periodontology 2000, 64, pp